BACKGROUND: Obesity is an important risk factor for cardiometabolic disease, including dyslipidemia and atherosclerotic cardiovascular disease. Although the role of the liver in dyslipidemia is established, the contribution of adipose tissue is less clear. This study aims to clarify the role of adipose tissue in lipid metabolism and dyslipidemia. METHODS: We conducted a cross-sectional analysis of 125 patients from the BARIA (The Immune System and Microbial Tone in Relation to NAFLD/NASH Before and After Bariatric Surgery in the Morbidly Obese in Amsterdam) longitudinal cohort study undergoing bariatric surgery. Comprehensive phenotyping included fasting untargeted plasma metabolomics, lipid, lipoprotein, adipokine profiling, RNA sequencing, and fecal shotgun metagenomics. Tissue transcriptomic and plasma metabolites were compared between individuals with and without dyslipidemia. RESULTS: Dyslipidemia was present in 43 of 125 individuals (34.4%), with higher triglycerides (1.62 versus 1.24 mmol/L), apoB (apolipoprotein B; 93.15 versus 81.81 mg/dL), and lower high-density lipoprotein (1.02 versus 1.35 mmol/L) and apoAI (136.40 versus 161.35 mg/dL). Plasma adipokines showed limited differences: leptin concentrations were lower in dyslipidemia in unadjusted analysis but reduced after adjustment for age, sex, and body weight (adjusted P=0.057). RNA sequencing identified altered gene expression of liver, jejunum, visceral and subcutaneous adipose tissue, most pronounced in subcutaneous adipose tissue. Dyslipidemia was associated with adipose tissue pathways related to inflammation, oxidative stress, and adipogenesis. Plasma metabolomics revealed associations with endocannabinoid-like, secondary bile acid, plasmalogen, butyrate, and sphingolipid metabolites. Gut metagenome analysis found modest differences. CONCLUSIONS: Dyslipidemia in obesity is associated with transcriptomic alterations in adipose tissue, including subcutaneous adipose tissue, involving inflammation, oxidative stress, and adipogenesis. These findings support a role of adipose tissue in lipid regulation beyond hepatic pathways.